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- Title
Genome-wide association study of nocturnal blood pressure dipping in hypertensive patients.
- Authors
Rimpelä, Jenni M.; Pörsti, Ilkka H.; Jula, Antti; Lehtimäki, Terho; Niiranen, Teemu J.; Oikarinen, Lasse; Porthan, Kimmo; Tikkakoski, Antti; Virolainen, Juha; Kontula, Kimmo K.; Hiltunen, Timo P.
- Abstract
Background: Reduced nocturnal fall (non-dipping) of blood pressure (BP) is a predictor of cardiovascular target organ damage. No genome-wide association studies (GWAS) on BP dipping have been previously reported. Methods: To study genetic variation affecting BP dipping, we conducted a GWAS in Genetics of Drug Responsiveness in Essential Hypertension (GENRES) cohort (<italic>n</italic> = 204) using the mean night-to-day BP ratio from up to four ambulatory BP recordings conducted on placebo. Associations with <italic>P</italic> < 1 × 10− 5 were further tested in two independent cohorts: Haemodynamics in Primary and Secondary Hypertension (DYNAMIC) (<italic>n</italic> = 183) and Dietary, Lifestyle and Genetic determinants of Obesity and Metabolic Syndrome (DILGOM) (<italic>n</italic> = 180). We also tested the genome-wide significant single nucleotide polymorphism (SNP) for association with left ventricular hypertrophy in GENRES. Results: In GENRES GWAS, rs4905794 near <italic>BCL11B</italic> achieved genome-wide significance (<italic>β</italic> = − 4.8%, <italic>P</italic> = 9.6 × 10− 9 for systolic and <italic>β</italic> = − 4.3%, <italic>P</italic> = 2.2 × 10− 6 for diastolic night-to-day BP ratio). Seven additional SNPs in five loci had <italic>P</italic> values < 1 × 10− 5. The association of rs4905794 did not significantly replicate, even though in DYNAMIC the effect was in the same direction (<italic>β</italic> = − 0.8%, <italic>P</italic> = 0.4 for systolic and <italic>β</italic> = − 1.6%, <italic>P</italic> = 0.13 for diastolic night-to-day BP ratio). In GENRES, the associations remained significant even during administration of four different antihypertensive drugs. In separate analysis in GENRES, rs4905794 was associated with echocardiographic left ventricular mass (<italic>β</italic> = − 7.6 g/m2, <italic>P</italic> = 0.02). Conclusions: rs4905794 near <italic>BCL11B</italic> showed evidence for association with nocturnal BP dipping. It also associated with left ventricular mass in GENRES. Combined with earlier data, our results provide support to the idea that <italic>BCL11B</italic> could play a role in cardiovascular pathophysiology.
- Subjects
BLOOD pressure; HYPERTENSION; CARDIOVASCULAR diseases; HEART beat; GENETIC polymorphisms
- Publication
BMC Medical Genetics, 2018, Vol 19, Issue 1, pN.PAG
- ISSN
1471-2350
- Publication type
Article
- DOI
10.1186/s12881-018-0624-7